The mutation responsible for Hutchinson Gilford Progeria Syndrome (HGPS) causes abnormal nuclear morphology. Previous studies show that free radicals and reactive oxygen species play major roles in the etiology and/or progression of neurodegenerative diseases and aging. This study compares oxidative stress responses between progeric and normal fibroblasts. Our data revealed higher ROS levels in HGPS cells compared to age-matched controls. In response to oxidative challenge, progeric cells showed increased mRNA levels for mitochondrial superoxide dismutase (SOD) and SOD protein content. However, this did not prevent a drop in the ATP content of progeria fibroblasts. Previous studies have shown that declines in human fibroblast ATP levels interfere with programmed cell death and promote necrotic inflammation. Notably, in our investigations the ATP content of progeria fibroblasts was only approximately 50% of that found in healthy controls. Furthermore, HGPS fibroblast analysis revealed a decrease in total caspase-like proteasome activity and in the levels of two active proteolytic complex subunits (beta(5) and beta(7)). A number of studies indicate that the molecular mechanisms causing accelerated aging in progeric patients also occur in healthy cells of older individuals. Thus, the results of this study may also help explain some of the cellular changes that accompany normal aging.

中文翻译：

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progerin 对 Hutchinson Gilford 早衰患者成纤维细胞中氧化蛋白积累的影响。

导致哈钦森吉尔福德早衰综合症 (HGPS) 的突变导致核形态异常。先前的研究表明，自由基和活性氧在神经退行性疾病和衰老的病因和/或进展中起主要作用。本研究比较了早衰和正常成纤维细胞之间的氧化应激反应。我们的数据显示，与年龄匹配的对照相比，HGPS 细胞中的 ROS 水平更高。为响应氧化挑战，早衰细胞的线粒体超氧化物歧化酶 (SOD) 和 SOD 蛋白含量的 mRNA 水平增加。然而，这并没有阻止早衰成纤维细胞 ATP 含量的下降。先前的研究表明，人类成纤维细胞 ATP 水平的下降会干扰程序性细胞死亡并促进坏死性炎症。尤其，在我们的研究中，早衰成纤维细胞的 ATP 含量仅为健康对照的 50% 左右。此外，HGPS 成纤维细胞分析显示总半胱天冬酶样蛋白酶体活性和两个活性蛋白水解复合物亚基（beta(5) 和 beta(7)）的水平下降。许多研究表明，导致早衰患者加速衰老的分子机制也发生在老年人的健康细胞中。因此，这项研究的结果也可能有助于解释伴随正常衰老的一些细胞变化。许多研究表明，导致早衰患者加速衰老的分子机制也发生在老年人的健康细胞中。因此，这项研究的结果也可能有助于解释伴随正常衰老的一些细胞变化。许多研究表明，导致早衰患者加速衰老的分子机制也发生在老年人的健康细胞中。因此，这项研究的结果也可能有助于解释伴随正常衰老的一些细胞变化。